@article{ef2e7d1d5f9642d38aa50a589e2007f8,
title = "Prospective longitudinal analysis of 2-hydroxyglutarate magnetic resonance spectroscopy identifies broad clinical utility for the management of patients with IDH-mutant glioma",
abstract = "Purpose: Proton magnetic resonance spectroscopy (MRS) of the brain can detect 2-hydroxyglutarate (2HG), the oncometabolite produced in neoplasms harboring a mutation in the gene coding for isocitrate dehydrogenase (IDH). We conducted a prospective longitudinal imaging study to determine whether quantitative assessment of 2HG by MRS could serve as a noninvasive clinical imaging biomarker for IDH-mutated gliomas. Patients and Methods: 2HG MRS was performed in 136 patients using point-resolved spectroscopy at 3 T in parallel with standard clinical magnetic resonance imaging and assessment. Data were analyzed in patient cohorts representing the major phases of the glioma clinical course and were further subgrouped by histology and treatment type to evaluate 2HG. Histologic correlations were performed. Results: Quantitative 2HG MRS was technically and biologically reproducible. 2HG concentration > 1 mM could be reliably detected with high confidence. During the period of indolent disease, 2HG concentration varied by less than ± 1 mM, and it increased sharply with tumor progression. 2HG concentration was positively correlated with tumor cellularity and significantly differed between high- and lower-grade gliomas. In response to cytotoxic therapy, 2HG concentration decreased rapidly in 1p/19q codeleted oligodendrogliomas and with a slower time course in astrocytomas and mixed gliomas. The magnitude and time course of the decrease in 2HG concentration and magnitude of the decrease in tumor volume did not differ between oligodendrogliomas treated with temozolomide or carmustine. Criteria for 2HG MRS were established to make a presumptive molecular diagnosis of an IDH mutation in gliomas technically unable to undergo a surgical procedure. Conclusion: 2HG concentration as measured by MRS was reproducible and reliably reflected the disease state. These data provide a basis for incorporating 2HG MRS into clinical management of IDH-mutated gliomas.",
author = "Changho Choi and Raisanen, {Jack M.} and Ganji, {Sandeep K.} and Song Zhang and McNeil, {Sarah S.} and Zhongxu An and Akshay Madan and Hatanpaa, {Kimmo J.} and Vamsidhara Vemireddy and Sheppard, {Christie A.} and Dwight Oliver and Hulsey, {Keith M.} and Vivek Tiwari and Tomoyuki Mashimo and James Battiste and Samuel Barnett and Madden, {Christopher J.} and Patel, {Toral R.} and Edward Pan and Malloy, {Craig R.} and Mickey, {Bruce E.} and Bachoo, {Robert M.} and Maher, {Elizabeth A.}",
note = "Funding Information: Supported by National Institutes of Health (NIH) Grants No. R21 CA159128 and R01 CA184584 (C.C.) and No. RC NS070675 and R01 CA154843 (E.A.M.), by NIH Resource Grant No. EB015908, by Simmons Cancer Center NIH Support Grant No. 5P30 CA142543, by Cancer Prevention Research Institute of Texas Grants No. RP130427 (C.C.) and No. RP130629 (E.A.M.), by Young Texans Against Cancer (R.M.B., E.A.M.), and by philanthropic funds from the Advanced Imaging Research Center, Annette G. Strauss Center for Neuro-Oncology, Miller Family Fund in Neuro-Oncology, and Gladie Jo Salvino Fund for Glioblastoma Research at the University of Texas Southwestern Medical Center. We thank the patients who participated in this study and highly value the time they spent in every scan. We acknowledge the collaboration, many discussions, and institutional support provided by Dean Sherry, PhD. We also thank Ivan Dimitrov, PhD, for technical assistance and Ingo Mellinghoff, MD, for productive discussions regarding the comparison of data obtained at University of Texas Southwestern with this method implemented at Memorial Sloan Kettering Cancer Center. We thank Jeannie Baxter, RN, for assistance with all phases of the research imaging study and Rani Varghese, Salvador Pena, and Lily Yang for expert care of the patients during research scans. We thank Michael Levy, APN, Calli Fanous, APN, Josie Sewell, APN, and Myriam Zoghbi, RN, for their expert assistance in identifying patients for the study and coordinating their clinical and research scans. We also thank Niccole Williams and Agatha Villegas for their expert assistance related to pathologic analysis, including sample identification and database management. Publisher Copyright: {\textcopyright} 2016 by American Society of Clinical Oncology.",
year = "2016",
month = nov,
day = "20",
doi = "10.1200/JCO.2016.67.1222",
language = "English (US)",
volume = "34",
pages = "4030--4039",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "33",
}